The fate of the cis and trans isomers of the pyrethroid insecticide cypermethrin (NRDC 149), a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate, has been studied in rats (1-5 mg/kg) by using three forms of radiolabeling (benzyl-14C, cyclopropyl-14C, and cyano-14C). Radioactivity derived from the benzyl-14C and cyclopropyl-14C labeling was rapidly eliminated, mostly in the urine. Tissue residues were generally very low, e.g., 0.01 pg/g in brain, with the exception of fat (~1 pg/g). Residues derived from the cis isomer tended to be higher than those derived from the trans isomer. The rate of depletion of the residues derived from [benzyl-14C] -cis-cypermethrin was rapid (tv2 was less than ~1 day) from all tissues except fat, from which radioactivity was eliminated with a half-life of [11][12] days. This residue was largely due to unchanged cis-cypermethrin. [cyono-14C]Cypermethrin afforded radioelimination and distribution characteristics similar to those reported for the cyanide ion.

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1. Following multiple oral administration of 14C-flocoumafen to rats at 0.02 and 0.1 mg/kg per week, appreciable cellular accumulation was seen in the liver. 2. Residues in the liver increased with dose throughout the duration of the experiment (14 weeks) at the low dose, but reached a plateau after 4 weeks at the high dose. The major component was unchanged flocoumafen together with a minor polar metabolite seen also in faeces. 3. The data suggest the presence in rat liver of a saturable high-affinity binding site for flocoumafen and a second binding site of lower affinity. 4. Lethal anticoagulant action occurs only when the binding sites have become saturated. 5. A range of haematological and clinical chemistry measurements failed to predict the onset of anticoagulant toxicity seen in the high dose treatment group. 6. Flocoumafen was not extensively metabolised; at the low dose, approximately 30% of the cumulative administered dose was eliminated in the faeces within 3 days of each dosing, mainly as unchanged rodenticide. At the high dose, this value ranged from 18% after the first dose to 59% after the tenth dose. 7. Two more polar metabolites and a lipophilic compound were minor products in faeces. Amounts of the polar products increased with cumulative dosage received. The urinary route of elimination was a very minor one (less than 1.6%) at both doses.

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1. The major metabolic transformation of orally ingested 14C-DGEBPA is by hydrolytic ring-opening of the two epoxide rings to form diols. This metabolite (the bis-diol of DGEBPA) is excreted in both free and conjugated forms and is further metabolized to various carboxylic acids, including two containing a methylsulphonyl moiety. 2. The product of oxidative dealkylation either of DGEBPA (with concomitant formation of glycidaldehyde) or of the bis-diol of DGEBPA (with concomitant formation of glyceraldehyde) is excreted in both free and conjugated forms in amounts representing 5% of the dose. 3. The high activity of epoxide hydratase towards DGEBPA suggests that glyceraldehyde and not glycidaldehyde is formed in vivo. 4. Hepatic epoxide hydratase activity towards DGEBPA measured in vitro decreased in the order rabbit greater than mouse greater than rat. 5. Two discrete epoxide hydratases are present in large amounts in the mouse. One is membrane-bound in the liver microsomal fraction and the other is a "soluble' enzyme located in the liver cytosol. This cytosolic enzyme was present in only very small amounts in the rat.

The metabolism of the pyrethroid insecticide cypermethrin has been studied in rats using three forms of 14C‐labelling (benzyl‐, cyclopropyl‐ and cyano‐) and separate cis‐ and trans‐ isomers. The proportion of the dose absorbed from the intestines (50–70% at 2–3 mg kg−1) is rapidly metabolised and eliminated. The major reaction is cleavage of the ester bond to afford the constituent cis‐ and trans‐ acids which are conjugated with glucuronic acid and eliminated in the urine. The 3‐phenoxybenzyl portion of the molecule is probably released as the α‐hydroxynitrile, which is converted via the aldehyde into 3‐phenoxybenzoic acid. This compound is then largely hydroxylated and eliminated as a sulphate conjugate. The cyanide ion is metabolised via predictable routes, for instance, as thiocyanate. Cypermethrin is hydroxylated to some extent before hydrolysis. Most of this hydroxylation occurs at the methyl group trans to the cyclopropane carboxyl group, and at the 4‐position of the phenoxy group. cis‐ Cypermethrin is slightly more stable than the trans‐isomer.

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